Researchers from UT Arlington suggest that two ruthenium-based complexes can be used to effectively control the growth of cancer cells without overt toxicities caused by traditional chemotherapeutic agents. The results of this study are published in Molecular Cancer Therapeutics.
Biochemistry and chemistry professor at The University of Texas at Arlington Dr. Fred MacDonnell has been investigating the role of metal based chemotherapeutic agents in collaboration with the researchers from City of Hope Comprehensive Center Duarte, California. The research teams contributed to develop a new anti-cancer therapy that can be used in combination with cisplatin.
Despite the fact that cisplatin is one of the most frequently prescribed anti-cancer therapies, the effectiveness of this drug as a chemotherapeutic agent is limited by its toxicity and resistance to certain cancers.
The research teams from UT Arlington conducted a series of experiments in pre-clinical lab testing of two newly developed ruthenium polypyridyl complexes and identified that these agents are as effective as cisplatin in the management of human non-small cell lung cancer cells. However, compared to cisplatin, the RPCs present a better pharmacodynamic and pharmacokinetic profile with better tolerance and no risk of toxicity, even when systemic normal cells are exposed to doses 10 times higher. Furthermore, RPCs function better in hypoxic conditions, hallmark of tumor cells.
Dr. MacDonnell commented:
“Cancer drugs on the market now generally are less effective under hypoxic conditions or insensitive to the oxygen concentration. Since many tumor cells are under hypoxic stress and most normal cells are not, having something that becomes even more effective under hypoxia could have some real benefit to the patient.”
The mode of activation of RPCs involves the redox activation of tatpp, a special portion of the drug molecule that increases the activity inside human cells and activates programmed cell death. Under conditions of low oxygen tension, the activation of drug is even higher resulting in higher cell death.
Dr. Sanjay Awasthi, professor of medical oncology and therapeutics research at City of Hope commented:
“Being activated under low-oxygen conditions makes these unique complexes excellent candidates for use on some of the most difficult to treat tumors. Now that we have demonstrated the role of the tatpp ligand in these biological processes, our team can continue toward the goal of using ruthenium-based complexes to enhance current treatments.”
MacDonnell suggested the enhanced activity of ruthenium complexes can be attributed to the ability of the complexes to enter cancer cells and induce cell death in metabolically active cells.